Cardiovascular Burden of the V142I Transthyretin Variant.

Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. Exposure: V142I carrier status (n = 754, 3.2%). Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

Impact of Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus on Offspring Cardiovascular Health in Early Adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), influence maternal cardiovascular heath (CVH) long after pregnancy, but their relationship to offspring CVH following in utero exposure remains uncertain. OBJECTIVE: To examine associations of HDP or GDM with offspring CVH in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study from 2000 to 2006 and the HAPO Follow-Up Study from 2013 to 2016. This analysis included 3,317 mother-child dyads from 10 field centers, comprising 70.8% of HAPO Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures were having any HDP or GDM compared with not having HDP or GDM, respectively (reference). The outcome was offspring CVH at ages 10 to 14 years, based on four metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The outcome was primarily defined as having at least one CVH metric that was non-ideal versus all ideal (reference), and secondarily as the number of non-ideal CVH metrics: at least one intermediate metric, one poor metric, or at least two poor metrics versus all ideal (reference). Modified Poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3,317 maternal-child dyads, the median (IQR) ages were 30.4 (25.6, 33.9) years for pregnant individuals and 11.6 (10.9, 12.3) years for children. During pregnancy, 10.4% of individuals developed HDP and 14.6% developed GDM. At follow-up, 55.5% of offspring had at least one non-ideal CVH metric. In adjusted models, having HDP (aRR 1.14; 95% CI 1.04, 1.25) or having GDM (aRR 1.10; 95% CI 1.02, 1.19) was associated with greater risk that offspring developed less-than-ideal CVH at ages 10 to 14 years. The above associations strengthened in magnitude as the severity of adverse CVH metrics increased (i.e., with the outcome measured as >1 intermediate, 1 poor, and >2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSONS: In this multi-national prospective cohort, pregnant individuals who experienced either HDP and GDM were at significantly increased risk of having offspring with worse CVH in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

BACKGROUND: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies. METHODS: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models. RESULTS: Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; P=1.77×10-5; JHS: hazard ratio, 1.25 [95% CI, 1.13-1.38]; P=6.38×10-6; hazard ratioexpressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors. CONCLUSIONS: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Adverse Pregnancy Outcomes and Predicted 30-Year Risk of Maternal Cardiovascular Disease 2-7 Years After Delivery.

OBJECTIVE: To determine whether adverse pregnancy outcomes are associated with a higher predicted 30-year risk of atherosclerotic cardiovascular disease (CVD; ie, coronary artery disease or stroke). METHODS: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. The exposures were adverse pregnancy outcomes during the first pregnancy (ie, gestational diabetes mellitus [GDM], hypertensive disorder of pregnancy, preterm birth, and small- and large-for-gestational-age [SGA, LGA] birth weight) modeled individually and secondarily as the cumulative number of adverse pregnancy outcomes (ie, none, one, two or more). The outcome was the 30-year risk of atherosclerotic CVD predicted with the Framingham Risk Score assessed at 2-7 years after delivery. Risk was measured both continuously in increments of 1% and categorically, with high predicted risk defined as a predicted risk of atherosclerotic CVD of 10% or more. Linear regression and modified Poisson models were adjusted for baseline covariates. RESULTS: Among 4,273 individuals who were assessed at a median of 3.1 years after delivery (interquartile range 2.5-3.7), the median predicted 30-year atherosclerotic CVD risk was 2.2% (interquartile range 1.4-3.4), and 1.8% had high predicted risk. Individuals with GDM (least mean square 5.93 vs 4.19, adjusted ß=1.45, 95% CI, 1.14-1.75), hypertensive disorder of pregnancy (4.95 vs 4.22, adjusted ß=0.49, 95% CI, 0.31-0.68), and preterm birth (4.81 vs 4.27, adjusted ß=0.47, 95% CI, 0.24-0.70) were more likely to have a higher absolute risk of atherosclerotic CVD. Similarly, individuals with GDM (8.7% vs 1.4%, adjusted risk ratio [RR] 2.02, 95% CI, 1.14-3.59), hypertensive disorder of pregnancy (4.4% vs 1.4%, adjusted RR 1.91, 95% CI, 1.17-3.13), and preterm birth (5.0% vs 1.5%, adjusted RR 2.26, 95% CI, 1.30-3.93) were more likely to have a high predicted risk of atherosclerotic CVD. A greater number of adverse pregnancy outcomes within the first birth was associated with progressively greater risks, including per 1% atherosclerotic CVD risk (one adverse pregnancy outcome: 4.86 vs 4.09, adjusted ß=0.59, 95% CI, 0.43-0.75; two or more adverse pregnancy outcomes: 5.51 vs 4.09, adjusted ß=1.16, 95% CI, 0.82-1.50), and a high predicted risk of atherosclerotic CVD (one adverse pregnancy outcome: 3.8% vs 1.0%, adjusted RR 2.33, 95% CI, 1.40-3.88; two or more adverse pregnancy outcomes: 8.7 vs 1.0%, RR 3.43, 95% CI, 1.74-6.74). Small and large for gestational age were not consistently associated with a higher atherosclerotic CVD risk. CONCLUSION: Individuals who experienced adverse pregnancy outcomes in their first birth were more likely to have a higher predicted 30-year risk of CVD measured at 2-7 years after delivery. The magnitude of risk was higher with a greater number of adverse pregnancy outcomes experienced.

Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Changes in Age Distribution and Maternal Mortality in a Subset of the US, 2014-2021.

INTRODUCTION: This study aimed to determine the association between changes in age distribution and maternal mortality rates (MMR) in a subset of the United States between 2014 and 2021. METHODS: A serial cross-sectional analysis of birthing individuals aged 15-44 years from 2014 to 2021 was performed. States that had not adopted the pregnancy checkbox as of 2014 were excluded from the primary analysis. A significant inflection point in MMR was identified in 2019 with the Joinpoint Regression Program, so all analyses were stratified: 2014-2019 and 2019-2021. The Kitagawa decomposition was applied to quantify the contribution from (1) changes in age distribution and (2) changes in age-specific MMR (ASMR) to total MMR. Data analysis occurred between 2022 and 2023. RESULTS: From 2014 to 2021, the mean (standard deviation) age of birthing individuals changed from 28.3 (5.8) to 29.4 (5.7) years. The MMR (95% CI) increased significantly from 16.5 (15.8-18.5) to 18.9 (17.4-20.5) per 100,000 live births from 2014 to 2019 with acceleration in MMR to 31.8 (30.0-33.8) by 2021. The change in maternal age distribution contributed to 36% of the total change in the MMR from 2014 to 2019 and 4% from 2019 to 2021. Age-specific MMR components increased significantly for those aged 25-29 years and 30-34 years from 2014 to 2019. All 5-year age strata except the 15-19 year old group saw increases in age-specific MMR from 2019 to 2021. CONCLUSIONS: MMR increased significantly from 2014 to 2021 with rapid increase after 2019. However, older age of birthing individuals explained only a minority of the increased MMR in both periods. The greatest contribution to MMR arose from increases in age-specific MMR.

Social and psychosocial determinants of racial and ethnic differences in cardiovascular health: The MASALA and MESA studies.

Background: Social and psychosocial determinants are associated with cardiovascular health (CVH). Objectives: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH. Methods: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants. Results: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 Chinese (CVH 9.69 [1.8]), 1,496 Hispanic (CVH 8.00 [2.1]), 1,164 South Asian (CVH 9.16 [2.0]), and 2,622 White (CVH 8.91 [2.1]) participants. The factors that were associated with the largest magnitude of explained differences in mean CVH score were income for Black participants (if mean income in Black participants were equal to White participants, Black participants' mean CVH score would be 0.14 [SE 0.05] points higher); place of birth for Chinese participants (if proportion of US-born and foreign-born individuals among Chinese adults were equivalent to White participants, Chinese participants' mean CVH score would be 0.22 [0.10] points lower); and education for Hispanic and South Asian participants (if educational attainment were equivalent to White participants, Hispanic and South Asian participants' mean CVH score would be 0.55 [0.11] points higher and 0.37 [0.11] points lower, respectively). Conclusions: In these multiethnic US cohorts, social and psychosocial factors were associated with racial/ethnic differences in CVH.

Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.

Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association.

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life's Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.

An Age-Period-Cohort Analysis of Cardiovascular Disease Mortality in the United States from 1999 to 2018.

BACKGROUND: Although cardiovascular disease mortality rates in the United States declined from the 1970s to 2010s, they have now plateaued. The independent effects of age, period, and birth year (cohort) on cardiovascular disease mortality have not previously been defined. METHODS: We used data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research to examine the effects of age, period, and cohort on cardiovascular disease mortality among individuals aged 20-84 years from 1999 to 2018, prior to the onset of the coronavirus disease 2019 pandemic. Age effects were described as cardiovascular disease-related mortality rates in each 5-year age group adjusted for year of death (period) and year of birth (cohort). Period and cohort effects were quantified as adjusted rate ratios (RRs) comparing cardiovascular disease mortality rates in each period and cohort to the reference periods and reference cohort (ie, 1919 birth cohort), respectively. RESULTS: Between 1999 to 2018, there were 10,404,327 cardiovascular disease deaths among US adults. In each individual birth cohort, the age-specific cardiovascular disease mortality rates were stable between ages 20 through 39 years. Age-specific rates were higher for each year older between ages 40 through 84 years adjusting for period effects. The period cardiovascular disease mortality rates were lower in later periods (2004-2008 period RR 0.87, 95% confidence interval [CI] 0.85 to 0.88; 2009-2013 period RR 0.78, 95% CI 0.76 to 0.80) compared with the reference period (1999 to 2003) and plateaued thereafter. The cohort cardiovascular disease mortality rates were progressively lower in more recent birth cohorts (1924 birth cohort RR 0.85, 95% CI 0.83 to 0.87; 1974 birth cohort RR 0.29, 95% CI 0.27 to 0.32) compared with the reference cohort (1919 cohort) and plateaued thereafter. CONCLUSION: Although cardiovascular disease mortality rates declined rapidly among those born between 1919 and 1974, improvements plateaued in birth cohorts thereafter even adjusted for period effects.

Prioritizing the primary prevention of heart failure: Measuring, modifying and monitoring risk.

With the rising incidence of heart failure (HF) and increasing burden of morbidity, mortality, and healthcare expenditures, primary prevention of HF targeting individuals in at-risk HF (Stage A) and pre-HF (Stage B) Stages has become increasingly important with the goal to decrease progression to symptomatic (Stage C) HF. Identification of risk based on traditional risk factors (e.g., cardiovascular health which can be assessed with the American Heart Association's Life's Essential 8 framework), adverse social determinants of health, inherited risk of cardiomyopathies, and identification of risk-enhancing factors, such as patients with viral disease, exposure to cardiotoxic chemotherapy, and history of adverse pregnancy outcomes should be the first step in evaluation for HF risk. Next, use of guideline-endorsed risk prediction tools such as Pooled Cohort Equations to Prevent Heart Failure provide quantification of absolute risk of HF based in traditional risk factors. Risk reduction through counseling on traditional risk factors is a core focus of implementation of prevention and may include the use of novel therapeutics that target specific pathways to reduce risk of HF, such as mineralocorticoid receptor agonists (e.g., fineronone), angiotensin-receptor/neprolysin inhibitors, and sodium glucose co-transporter-2 inhibitors. These interventions may be limited in at-risk populations who experience adverse social determinants and/or individuals who reside in rural areas. Thus, strategies like telemedicine may improve access to preventive care. Gaps in the current knowledge base for risk-based prevention of HF are highlighted to outline future research that may target approaches for risk assessment and risk-based prevention with the use of artificial intelligence, genomics-enhanced strategies, and pragmatic trials to develop a guideline-directed medical therapy approach to reduce risk among individuals with Stage A and Stage B HF.

Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis.

Left ventricular (LV) systolic dysfunction represents a highly treatable cause of heart failure (HF). A substantial proportion of patients with HF with reduced ejection fraction (EF;HFrEF) demonstrate improvement in LV systolic function (termed HF with improved EF [HFimpEF]), either spontaneously or when treated with guideline-directed medical therapy (GDMT). Although it is a relatively new HF classification, HFimpEF has emerged in recent years as an important and distinct clinical entity. Improvement in LVEF leads to decreased rates of mortality and adverse HF-related outcomes compared to patients with sustained LV systolic dysfunction (HFrEF). While numerous clinical and imaging factors have been associated with HFimpEF, identification of which patients do and do not improve requires further investigation. In addition, patients improve at different rates, and what determines the trajectory of HFimpEF patients after improvement is incompletely characterized. A proportion of patients maintain improvement in LV systolic function, while others experience a recrudescence of systolic dysfunction, especially with GDMT discontinuation. In this review we discuss the contemporary guideline-recommended classification definition of HFimpEF, the epidemiology of improvement in LV systolic function, and the clinical course of this unique patient population. We also offer evidence-based recommendations for the clinical management of HFimpEF and provide a roadmap for future directions in understanding and improving outcomes in the care of patients with HFimpEF.

Proteomic Biomarkers of Quantitative Interstitial Abnormalities in COPDGene and CARDIA Lung Study.

Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts. Methods: We measured the plasma proteomics of 4,383 participants in an older, ever-smoker cohort (COPDGene [Genetic Epidemiology of Chronic Obstructive Pulmonary Disease]) and 2,925 participants in a younger population cohort (CARDIA [Coronary Artery Disease Risk in Young Adults]) using the SomaLogic SomaScan assays. We measured QIAs using a local density histogram method. We assessed the associations between proteomic biomarker concentrations and QIAs using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, and study center (Benjamini-Hochberg false discovery rate-corrected P ⩽ 0.05). Measurements and Main Results: In total, 852 proteins were significantly associated with QIAs in COPDGene and 185 in CARDIA. Of the 144 proteins that overlapped between COPDGene and CARDIA, all but one shared directionalities and magnitudes. These proteins were enriched for 49 Gene Ontology pathways, including biological processes in inflammatory response, cell adhesion, immune response, ERK1/2 regulation, and signaling; cellular components in extracellular regions; and molecular functions including calcium ion and heparin binding. Conclusions: We identified the proteomic biomarkers of QIAs in an older, smoking population with a higher prevalence of pulmonary disease and in a younger, healthier community cohort. These proteomics features may be markers of early precursors of advanced lung diseases.

Effect of early medication adherence on behavioral treatment utilization and smoking cessation among individuals with current or past major depressive disorder.

SIGNIFICANCE: Little is known about the mechanisms by which medication adherence promotes smoking cessation among adults with MDD. We tested the hypothesis that early adherence promotes abstinence by increasing behavioral treatment (BT) utilization. METHODS: Data for this post-hoc analysis were from a randomized trial of 149 adults with current or past MDD treated with BT and either varenicline (n = 81) or placebo (n = 68). Arms were matched on medication regimen. Early medication adherence was measured by the number of days in which medication was taken at the prescribed dose during the first six of 12 weeks of pharmacological treatment (weeks 2-7). BT consisted of eight 45-minute sessions (weeks 1-12). Bioverified abstinence was assessed at end-of-treatment (week 14). A regression-based approach was used to test whether the effect of early medication adherence on abstinence was mediated by BT utilization. RESULTS: Among 141 participants who initiated the medication regimen, BT utilization mediated the effect of early medication adherence on abstinencea) an interquartile increase in early medication days from 20 to 42 predicted a 4.2 times increase in abstinence (Total Risk Ratio (RR) = 4.24, 95% CI = 2.32-13.37; p <.001); b) increases in BT sessions predicted by such an increase in early medication days were associated with a 2.7 times increase in abstinence (Indirect RR = 2.73, 95% CI = 1.54-7.58; p <.001); and c) early medication adherence effects on abstinence were attenuated, controlling for BT (Direct RR = 1.55, 95% CI = 0.83-4.23, p =.17). CONCLUSIONS: The effect of early medication adherence on abstinence in individuals with current or past MDD is mediated by intensive BT utilization.